Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen in the U.S. with an estimated 10 million cases annually. Studies have been carried out to further define the clinical spectrum of chlamydial infection, to develop rapoid diagnostic assays, and to examine the pathogenesis of chlamydial infections in experimental animal models. In a study of 704 homosexual men at risk for AIDS, 7.5% had rectal chlamydial infections. Men with chlamydia were more likely to be HIV seropositive (48%) than men without chlamydial infection (25%), to have fewer T helper cells, and to have a mucopurulent exudate. Chlamydial infection rates were markedly increased in those with symptomatic proctitis (12%) and with AIDS (14%). In women, chlamydia cervical infection continues to be high (20%). Coinfection with gonorrhea and human papillomavirus is being examined in relationship to cervical dysplasia and cervical carcinoma by culture and in situ hybridization techniques. The reliability of in situ hybridization utilizing DNA and RNA probes for C. trachomatis has been demonstrated in tissue biopsies from infected animals and patients. Development of a primate model of rectal C. trachomatis lymphogranuloma venereum (LGV) infection and respiratory chlamydia-TWAR infection has aided in the study of the mucosal immune response to chlamydial infection. In LGV infection, antigen-reactive T cells are present in the gut mucosa. The administration of cyclosporine inhibited the primary antibody and proliferative response of peripheral blood lymphocytes, but did not prevent the expansion of antigen- specific mucosal and spleen lymphocyte populations. In summary, the above studies demonstrate the diverse clinical spectrum of C. trachomatis and provide methods for study of the immunopathogenesis of chlamydial infection.